RT Journal Article
SR Electronic
T1 Sir2-Dependent Activation of Acetyl-CoA Synthetase by Deacetylation of Active Lysine
JF Science
JO Science
FD American Association for the Advancement of Science
SP 2390
OP 2392
DO 10.1126/science.1077650
VO 298
IS 5602
A1 Starai, V. J.
A1 Celic, I.
A1 Cole, R. N.
A1 Boeke, J. D.
A1 Escalante-Semerena, J. C.
YR 2002
UL http://science.sciencemag.org/content/298/5602/2390.abstract
AB Acetyl-coenzyme A (CoA) synthetase (Acs) is an enzyme central to metabolism in prokaryotes and eukaryotes. Acs synthesizes acetyl CoA from acetate, adenosine triphosphate, and CoA through an acetyl–adenosine monophosphate (AMP) intermediate. Immunoblotting and mass spectrometry analysis showed thatSalmonella enterica Acs enzyme activity is posttranslationally regulated by acetylation of lysine-609. Acetylation blocks synthesis of the adenylate intermediate but does not affect the thioester-forming activity of the enzyme. Activation of the acetylated enzyme requires the nicotinamide adenine dinucleotide–dependent protein deacetylase activity of the CobB Sir2 protein from S. enterica. We propose that acetylation modulates the activity of all the AMP-forming family of enzymes, including nonribosomal peptide synthetases, luciferase, and aryl- and acyl-CoA synthetases. These findings extend our knowledge of the roles of Sir2 proteins in gene silencing, chromosome stability, and cell aging and imply that lysine acetylation is a common regulatory mechanism in eukaryotes and prokaryotes.